Orlandi Matteo, Macchiagodena Marina, Procacci Piero, Carta Fabrizio, Supuran Claudiu T, Pagliai Marco
Dipartimento di Chimica "Ugo Schiff", Università degli Studi di Firenze, Florence, Italy.
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Sezione di Scienze Farmaceutiche, Università degli Studi di Firenze, Florence, Italy.
J Comput Chem. 2025 Jun 15;46(16):e70154. doi: 10.1002/jcc.70154.
We developed and validated a novel force field in the context of the AMBER parameterization for the simulation of cadmium(II)-binding proteins. The proposed force field takes into account the polarization effect produced by the central ion on its surroundings. The new polarized atomic charges for cysteine and histidine residues were derived based on the available structures of cadmium-bearing proteins using QM calculations and QM/MM simulations. The developed force field was validated by performing molecular dynamics simulations on several cadmium(II)-binding proteins. Our model preserves the tetra-coordination of the metal site with remarkable stability, yielding mean distances between ion and S or N atoms of the binding residues in close agreement with experimental data.
我们在AMBER参数化的背景下开发并验证了一种用于模拟镉（II）结合蛋白的新型力场。所提出的力场考虑了中心离子对其周围环境产生的极化效应。基于含镉蛋白质的现有结构，通过量子力学（QM）计算和QM/MM模拟得出了半胱氨酸和组氨酸残基的新极化原子电荷。通过对几种镉（II）结合蛋白进行分子动力学模拟，验证了所开发的力场。我们的模型以显著的稳定性保持了金属位点的四面体配位，离子与结合残基的S或N原子之间的平均距离与实验数据非常吻合。
